Evaluating the Role of Immune Responses in the Emergence of Protease Inhibitor Mutations

Objective 1: Evaluate the role of the immune responses in determining the emergence of HCV
NS3 resistance mutation during protease inhibitor therapy

Hypothesis 1 (HT 1): Low HLA binding to peptides containing protease inhibitor resistance
mutations is associated with the emergence of protease inhibitor mutants during therapy and
failure of the treatment.

Hypothesis 2 (HT 2): A hole in T cell repertoire may allow emergence of protease inhibitor
mutants during protease inhibitor therapy which leads to loss of the immune responses to
these mutants and failure of treatment.

Inclusion Criteria: All chronically HCV-infected patients who fail peg-IFN and RBV therapy
and are eligible for combined treatment with PI therapy will be enrolled. Briefly, this
includes:

1. Male or female

2. Age 18 to 65

3. Chronic HCV infection evidenced by liver biopsy or persistent HCV viremia for >6
months

4. Treatment experienced and classified as non-responder or relapser to prior
interferon-based therapy.

Exclusion criteria:

1. Treatment naïve chronically HCV-infected patients.

2. Patients with a history of inflammatory bowel diseases (IBD) or suspected IBD,
autoimmune diseases, including rheumatoid arthritis, and any patients on systemic
immunomodulators.

3. Pregnancy

4. HIV